PMID- 34169200 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220424 IS - 2468-0249 (Electronic) IS - 2468-0249 (Linking) VI - 6 IP - 6 DP - 2021 Jun TI - Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults. PG - 1603-1613 LID - 10.1016/j.ekir.2021.03.884 [doi] AB - INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare, complex, multisystem disease of dysregulated complement activity, characterized by progressive thrombotic microangiopathy (TMA), acute kidney injury, and multiorgan dysfunction, which often progresses to chronic kidney disease. Results from the prospective clinical trial of ravulizumab (NCT02949128) reveal rapid resolution of TMA in patients with aHUS, with sustained efficacy and safety in a 26-week initial evaluation period. METHODS: The aim of this analysis was to characterize the long-term efficacy and the safety profile of ravulizumab in adults with aHUS who had completed the initial evaluation period of the trial. Complete TMA response, hematologic and kidney functions, and safety were evaluated for all patients available for follow-up in the extension period (median follow-up: 76.7 weeks; range: 0.6-118.3). This trial included a total of 58 patients, 49 of whom entered the extension period. RESULTS: A total of 4 additional patients achieved complete TMA response during the follow-up period. Normalization of platelet count, serum lactate dehydrogenase (LDH), and hemoglobin observed in the 26-week initial evaluation period was sustained until the last available follow-up, as were the improvements in the estimated glomerular filtration rate (eGFR) and patient quality of life. All efficacy endpoints were correlated with the sustained inhibition of complement C5. Most adverse events (AEs) occurred early during the initial evaluation period and decreased substantially during the extension period. No patient developed a meningococcal infection or died during the extension period. CONCLUSION: This analysis reveals that ravulizumab administered every 8 weeks is efficacious with an acceptable safety profile for the long-term treatment of adults with aHUS and provides additional clinical benefit beyond 6 months of treatment. CI - (c) 2021 Published by Elsevier, Inc., on behalf of the International Society of Nephrology. FAU - Barbour, Thomas AU - Barbour T AD - Kidney Care, The Royal Melbourne Hospital, Melbourne, Australia. FAU - Scully, Marie AU - Scully M AD - Department of Haematology, University College London Hospitals, London, UK. FAU - Ariceta, Gema AU - Ariceta G AD - Paediatric Nephrology Department, University Hospital Vall d'Hebron, Barcelona, Spain. FAU - Cataland, Spero AU - Cataland S AD - Division of Hematology, The Ohio State University Medical Center, Columbus, Ohio, USA. FAU - Garlo, Katherine AU - Garlo K AD - Clinical Development, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, USA. FAU - Heyne, Nils AU - Heyne N AD - Section of Nephrology and Hypertension, Tubingen University Hospital, Tubingen, Germany. FAU - Luque, Yosu AU - Luque Y AD - Intensive Care Nephrology and Transplantation Department, APHP, Sorbonne Universite, Paris, France. FAU - Menne, Jan AU - Menne J AD - KRH Klinikum Mitte-Location Siloah, Hannover, Germany. FAU - Miyakawa, Yoshitaka AU - Miyakawa Y AD - Department of General Internal Medicine, Saitama Medical University, Saitama, Japan. FAU - Yoon, Sung-Soo AU - Yoon SS AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. FAU - Kavanagh, David AU - Kavanagh D AD - Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. AD - National Renal Complement Therapeutics Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK. CN - 311 Study Group Members LA - eng PT - Journal Article DEP - 20210324 PL - United States TA - Kidney Int Rep JT - Kidney international reports JID - 101684752 PMC - PMC8207473 OTO - NOTNLM OT - *atypical hemolytic uremic syndrome OT - *complement OT - *hemolytic uremic syndrome OT - *kidney failure OT - *ravulizumab OT - *thrombotic microangiopathy FIR - Babu, Sunil IR - Babu S FIR - Broeders, Nilufer IR - Broeders N FIR - Lietar, Nicole IR - Lietar N FIR - Brown, Fiona IR - Brown F FIR - Campbell, Philip IR - Campbell P FIR - Campistol, Josep M IR - Campistol JM FIR - Chowdhury, Paramit IR - Chowdhury P FIR - Kasimatis, Theo IR - Kasimatis T FIR - Cirami, Lino IR - Cirami L FIR - Caroti, Leonardo IR - Caroti L FIR - Antognoli, Guilia IR - Antognoli G FIR - Delmas, Yahsou IR - Delmas Y FIR - Dobronravov, Vladimir IR - Dobronravov V FIR - Gaeckler, Anja IR - Gaeckler A FIR - Garrouste, Cyril IR - Garrouste C FIR - Greenwood, Gregory IR - Greenwood G FIR - Griffin, Sian IR - Griffin S FIR - Huang, Chiu-Ching IR - Huang CC FIR - Chen, I-Ru IR - Chen IR FIR - Huang, Susan IR - Huang S FIR - Kim, Jin Seok IR - Kim JS FIR - La Manna, Gaetano IR - La Manna G FIR - Le Quintrec, Moglie IR - Le Quintrec M FIR - Jeantet, Guillaume IR - Jeantet G FIR - Fumie, Iino IR - Fumie I FIR - Rondeau, Eric IR - Rondeau E FIR - Haller, Hermann IR - Haller H FIR - Morelle, Johan IR - Morelle J FIR - Goffin, Eric IR - Goffin E FIR - Muhlfeld, Anja IR - Muhlfeld A FIR - Nagaraj, Shashi IR - Nagaraj S FIR - Arepally, Gowthami IR - Arepally G FIR - Oh, Doyeun IR - Oh D FIR - Okumi, Masayoshi IR - Okumi M FIR - Terente, Manuel Praga IR - Terente MP FIR - Provot, Francois IR - Provot F FIR - Schonermarck, Ulf IR - Schonermarck U FIR - Fischereder, Michael IR - Fischereder M FIR - Terrada, Natalia Ramos IR - Terrada NR FIR - Seitz-Polski, Barbara IR - Seitz-Polski B FIR - Favre, Guillaume IR - Favre G FIR - Boyer-Suavet, Sonia IR - Boyer-Suavet S FIR - Vinogradova, Maria IR - Vinogradova M FIR - Kirsanova, Tatiana IR - Kirsanova T FIR - Wong, Edwin Ks IR - Wong EK EDAT- 2021/06/26 06:00 MHDA- 2021/06/26 06:01 PMCR- 2021/03/24 CRDT- 2021/06/25 06:56 PHST- 2020/12/23 00:00 [received] PHST- 2021/03/10 00:00 [revised] PHST- 2021/03/15 00:00 [accepted] PHST- 2021/06/25 06:56 [entrez] PHST- 2021/06/26 06:00 [pubmed] PHST- 2021/06/26 06:01 [medline] PHST- 2021/03/24 00:00 [pmc-release] AID - S2468-0249(21)01032-9 [pii] AID - 10.1016/j.ekir.2021.03.884 [doi] PST - epublish SO - Kidney Int Rep. 2021 Mar 24;6(6):1603-1613. doi: 10.1016/j.ekir.2021.03.884. eCollection 2021 Jun.